A research program is proposed to develop and validate a continuous glucose sensing system for the treatment and management of diabetes. The central sensing element is a miniature near infrared spectrometer that is integrated within a customized microfluidic chamber. An ultrafiltration probe collects a sample of interstitial fluid from the subcutaneous space and this sample is carried to an optimized spectrometer cell, where a 16 cm-1 resolution near infrared spectrum is collected over a spectral range of 4600 - 4200 cm-1 (2.17 - 2.38 um). A multivariate calibration model will be used to extract the glucose concentration from the resulting spectrum. An innovative feature of this research plan is the construction of both optical sources and detectors with ideal characteristics for this specific spectral range. These sources and detectors will be produced from novel semiconductor materials that will be synthesized by molecular beam epitaxy. Unique semiconductor heterostructure materials will be generated to produce materials with the optical properties necessary for measuring clinically relevant levels of glucose in samples of interstitial fluid. The combination of a sturdy spectrometer design and a robust ultrafiltration sampling system will make possible continuous operation over several days. Development of a custom electronics package is also proposed in order to control the system components and to broadcast the spectral information to a remote receiver. The goal is to produce a self-contained continuous glucose monitor, which can be used as either a nocturnal alarm or a continuous glucose monitor. Both in vitro and in vivo validation experiments are described to fully characterize the proposed analytical system. The talents of eleven researchers will be combined to provide expertise in the critical areas of chemical sensors, near infrared spectroscopy, chemometrics, microfluidics, microfabrication, biomedical ultrafiltration, semiconductor optical materials, semiconductor material synthesis by molecular beam epitaxial growth, optical device fabrication, electronics, wireless communications, and system evaluation in both animal models and human subjects.